Cancer Risk Stratification of Indeterminate Thyroid Nodules: A Cytological Approach

Background: Management recommendations for thyroid nodules rely primarily on the cytological diagnosis. However, 25% of biopsies render an indeterminate cytology for which management decision is more challenging due to heterogeneity of the specimens. This study aimed to stratify the cancer risk through subcategorization of indeterminate cytology. Methods: The indeterminate cytological specimens (Bethesda-III or IV) of 518 thyroid nodules consecutively evaluated at our academic cancer center between October 2008 and September 2015, blinded to the histological outcome, were retrospectively reviewed. Cytological specimens were subclassified into four groups: aspirates exhibiting nuclear atypia (n=158; 31%); architectural atypia (n=222; 43%); oncocytic features (n=120; 23%); or other types of atypia (n=18; 3%). The prevalence of malignancy and odds ratio for malignancy were calculated in 323 nodules with histological confirmation. Results: The prevalence of malignancy was 26% overall (20% in Bethesda-III and 29% in Bethesda-IV; p=0.07), and 47%, 12%, 24%, and 25% for aspirates with nuclear atypia, architectural atypia, oncocytic features, or other types of atypia, respectively. The OR of nuclear atypia over architectural atypia was 6.4 (3.4-12.2; p<0.001), and 2.7 over oncocytic features (1.4-5.1; p=0.01), whereas the OR of architectural atypia over oncocytic features was 0.4 (0.2-0.9; p=0.03). Results were similar for Bethesda-III and IV aspirates when analyzed independently. Furthermore, cytological subcategories improved cytology-histology correlation, as they were associated with distinct profiles of histological diagnoses (p<0.001). Conclusions: Cytological subcategories can effectively stratify the risk of malignancy of thyroid nodules with indeterminate cytology and improve cytology-histology correlation.